Mandic-Maravic Vanja, Mitkovic-Voncina Marija, Pljesa-Ercegovac Marija, Savic-Radojevic Ana, Djordjevic Miroslav, Ercegovac Marko, Pekmezovic Tatjana, Simic Tatjana, Pejovic-Milovancevic Milica
Institute of Mental Health, Belgrade, Serbia.
Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Front Psychiatry. 2021 Jun 25;12:672389. doi: 10.3389/fpsyt.2021.672389. eCollection 2021.
Autism spectrum disorders (ASD) are a heterogeneous group of developmental disorders, with different levels of symptoms, functioning, and comorbidities. Recent findings suggested that oxidative stress and genetic variability in glutathione S-transferases (GSTs) might increase the risk of ASD development. We aimed to determine whether GST polymorphisms influence the severity of symptoms as well as the cognitive and adaptive abilities in children with ASD. The sample included 113 ASD cases. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The clinical characteristics were determined with Autism Diagnostic Interview-Revised (ADI-R) in all of the participants. In non-verbal participants, we explored the adaptive functioning using the Vineland Adaptive Behavior Scale II, while in verbal participants, we used the Wechsler Abbreviated Scale of Intelligence (WASI). It was shown that the genotype was a predictor of a lower non-verbal communication impairment as well as of a lower chance of having seizures during life. genotype predicted a higher adaptive functioning. The predictive effect of , and genotype was moderated by exposure during pregnancy (maternal smoking and medication). The genotype was significantly associated to a better cognitive functioning in children with ASD. Besides the complex gene-environment interaction for the specific risk of developing ASD, there is also a possible complexity of interactions between genetic and environmental factors influencing the level of symptoms and impairment in people with ASD. Detoxification and antioxidant enzymes, such as GSTA1, might contribute to the core of this complexity.
自闭症谱系障碍(ASD)是一组异质性发育障碍,具有不同程度的症状、功能和共病情况。最近的研究结果表明,氧化应激和谷胱甘肽S-转移酶(GSTs)的基因变异性可能会增加ASD发生的风险。我们旨在确定GST基因多态性是否会影响ASD儿童的症状严重程度以及认知和适应能力。样本包括113例ASD病例。所有参与者均对GSTA1、GSTM1、GSTT1和GSTP1基因多态性进行了基因分型。所有参与者均使用修订版自闭症诊断访谈量表(ADI-R)确定临床特征。对于非言语参与者,我们使用文兰适应行为量表第二版来探究其适应功能,而对于言语参与者,我们使用韦氏儿童智力量表简式版(WASI)。结果显示, 基因型是较低非言语交流障碍以及一生中较低癫痫发作几率的预测指标。 基因型预测了较高的适应功能。 、 和 基因型的预测作用受到孕期暴露(母亲吸烟和用药)的调节。 基因型与ASD儿童更好的认知功能显著相关。除了特定的基因-环境相互作用导致ASD发生的复杂风险外,在影响ASD患者症状水平和损伤程度方面,遗传和环境因素之间也可能存在相互作用的复杂性。解毒和抗氧化酶,如GSTA1,可能是这种复杂性的核心因素。